Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice.
Arginine methylation has been implicated in the regulation of gene expression. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) binds the p160 family of steroid receptor coactivators (SRCs). This association enhances transcriptional activation by nuclear receptors. Here, we show that embryos with a targeted disruption of CARM1 are small in size and die perinatally. The methylation of two known CARM1 substrates, poly(A)-binding protein (PABP1) and the transcriptional cofactor p300, was abolished in knockout embryos and cells. However, CARM1-dependent methylation of histone H3 was not observed. Furthermore, estrogen-responsive gene expression was aberrant in Carm1-/- fibroblasts and embryos, thus emphasizing the role of arginine methylation as a transcription activation tag. These findings provide genetic evidence for the essential role of CARM1 in estrogen-mediated transcriptional activation.
Pubmed ID: 12756295 RIS Download
Amino Acid Sequence | Animals | Base Sequence | Cells, Cultured | E1A-Associated p300 Protein | Gene Expression | Genes, Lethal | Methylation | Mice | Mice, Knockout | Molecular Sequence Data | Nuclear Proteins | Poly(A)-Binding Protein I | Protein-Arginine N-Methyltransferases | Trans-Activators